(a) Technical Field
The present invention relates to a device for observing a sentinel lymph node (SLN) in a human body. More particularly, the present invention relates to a device for observing an SLN by detecting near-infrared (NIR) fluorescence caused by a fluorescent material such as indocyanine green (ICG) at the SLN and a method for detecting NIR fluorescence at an SLN.
(b) Background Art
Sentinel lymph node (SLN) is a lymph node that cancer cells firstly reach when the tumor is directly metastasized via lymph nodes. SLN biopsy is a method for identifying metastasis by finding an SLN through injection of a color pigment into cancer tissue, excising the SLN and then performing a histopathologic examination on the excised SLN. If a cancer is detected in the SLN, all lymph nodes around the cancer are excised. However, if the cancer is not detected in the SLN, it is determined that the cancer is not metastasized to the SLN, and the excision of the SLN can be minimized.
As such, the SLN biopsy can minimize, through minimum excision of lymph nodes, side effects and complications, which may be generated by completely excising peripheral lymph nodes together with cancer tissues in the existing operations. The SLN biopsy has been already performed as a standard surgical technique in breast cancer, melanoma, etc. In addition, the SLN biopsy is being extended to surgical operations in the fields of all cancers including lung cancer, esophageal cancer, stomach cancer, thyroid cancer, gynecological cancer, urologic cancer, laryngeal cancer, etc.
In the SLN biopsy, the position of the SLN cannot be exactly detected with the naked eye. Hence, a nuclear medicine imaging method using a radioactive isotope as a tracer, an imaging method using a magnetic fluid having magnetism, an optical imaging method using a vital dye, or a method simultaneously using a radioactive isotope and a vital dye is used in the SLN biopsy.
An optical imaging method and various fluorescent materials as vital dyes have been studied to minimize radiation exposure to a patient and to detect the SLN. For example, studies on an optical imaging probe for SLN detection including a poly-gamma-glutamic acid and an optical imaging dye complex have been conducted. Among fluorescent dyes, the use of indocyanine green (ICG) is permitted in many countries including FDA in USA. The ICG allows light to be excited in a near-infrared (NIR) region, and generates fluorescent light. In addition, the internal structure of human tissue distributed up to a depth of 10 to 20 mm can be observed using the ICG, and NIR fluorescent light can be observed even at a place where white visible light is thrown, such as an operating room.
However, such an NIR fluorescent dye cannot be seen with the naked eyes, and thus devices capable of observing NIR fluorescent light have been developed. As a result, a device called hyper eye medical system (HEMS) was recently developed for observing NIR during surgery.
The HEMS device is an imaging device for observing ICG fluorescent light. The HEMS device simultaneously measures visible light and NIR using a single camera 3 installed therein, and NIR fluorescent light can be observed even in an environment with bright external illumination. The HEMS device is shown in FIG. 1.
The HEMS device employs, together with a white light source 1, a light source (NIR LED) having a wavelength of 760 nm as an excitation light source 2. However, through the device having the structure described above, the external appearance of an opened organ can be seen only during an abdominal surgery, and there often occurs a confusion among the color of visible light, an ICG fluorescent image in an NIR combined image and an image caused by glare of white light reflected on the surface of a human body.
Meanwhile, Japanese Patent Application Publication No. 2006-340796 has disclosed a system for detecting an SLN from a fluorescent image. Particularly, in Japanese Patent Application Publication No. 2006-340796, white light including excitation light is emitted by a xenon lamp, and an excitation light filter is set to allow light of a wavelength band of 385 to 435 nm to be transmitted therethrough. In the case of fluorescent light and background light, obtained from an object to be measured, a light-shielding filter is inserted between an object to be observed and a single CCD chip to allow the fluorescent light and the background light to be transmitted therethrough. Thus, an image is picked up in the CCD chip. In addition, the image is processed by a TV camera to be shown as a fluorescent image through a monitor. However, the system is a device for a contrast medium which emits fluorescent light in visible light such as 5-ALA. The device is not suitable for observing fluorescent light in NIR, such as ICG.
In relation to this, U.S. Patent Application Publication No. 2011/0063427 discloses an imaging system for providing full-color reflection light and NIR image. The imaging system for obtaining the NIR and full-color image includes a light source which supplies visible light and NIR light to an object to be observed, and a camera having a plurality of image sensors which independently detect blue reflection light and green reflection light from the object to be observed, and alternately detect red reflection light and NIR light generated from the object to be observed.
A controller for transmitting a signal to the light source and the camera controls consecutive blue and green lights to be irradiated onto the object to be observed, and red light and NIR excitation light are synchronized by periodically switching on-off the light source and the camera so that red and NIR fluorescent images are alternately obtained from the camera.
A red reflection light spectrum and an NIR light spectrum are alternately obtained from the same image sensor through the switching synchronization between the light source and the camera. Thus, the red reflection light spectrum provides, together with the blue and green reflection lights, a full-color image, or the NIR light spectrum provides an NIR fluorescent image. However, the synchronization between the light source and the camera makes the device complicated.
Meanwhile, in an imaging system for simultaneously observing a wide range of spectra from visible light (400 to 700 nm) to NIR light (700 to 900 nm), a chromatic aberration correction is required to adjust the focus on the focal plane of an image obtaining chip such as a CCD sensor. U.S. Patent Application Publication No. US2011/0249323 A1 discloses a special optical coupler for correcting a chromatic aberration in an endoscope device. The disclosed optical coupler is configured with an afocal prism assembly and an imaging optics. The afocal prism assembly is configured with prisms having different refractive indices, and dichroic coating is performed at the boundary between the prisms, so that an incident wavelength is incident onto an appropriate prism. The chromatic aberration between visible light and NIR light, which pass through prisms having different refractive indices, is corrected by correcting the difference in light path length between the visible light and the NIR light. However, a specific optical system is required to remove the chromatic aberration in such a manner, and the existing optical couplers cannot be used.
In addition, when a visible light image and an NIR image are respectively displayed in two different screen windows of the same monitor or when the two images are displayed to overlap with each other, it is difficult to distinguish the visible light image from the NIR image.
Basically, the distinguishment of the SLN from a non-SLN depends on the intensity of a fluorescent signal. Even when the same device is used, the intensity of the fluorescent signal is considerably changed depending on a distance to an object to be observed, parameters (gain, shutter and frame) set in the detection sensitivity of a TV system, the intensity of excitation light, etc. Therefore, a standard measuring method is essentially required to ensure the reliability of a detection result.